Figures and References

Delayed-type
hypersensitivity (DTH),
cytotoxicity
Humoral immunity
Influence of immunological factors
including cytokines
T-cell-mediated
autoimmunity,
graft rejection
Allergy, antibody-mediated
autoimmune diseases,
tolerance
Th1 cell
Th2 cell
Figure .. A Model to Illustrate the Complex Balance between T helper 1(Th1) and
Th2 Cells
Harber, M., Sundstedt, A., and Wraith, D. (2000). The Role of Cytokines in Immunological
Tolerance: Potential for Therapy. Expert Reviews in Molecular Medicine, 2(9), 1–20. © Cambridge
Journals, reproduced with permission.
REFERENCES
Bamias, G., Martin, C., & Marini, M. (2003). Expression, localization and functional
activity of TL1A, a novel Th1-polarizing cytokine in inflammatory bowel disease.
J Immunol, 171, 4868–4874.
Bartel, G., Weiss, I., Turetschek, K., et al. (2008). Ingested matter affects intestinal
lesions in Crohn’s disease. Inflamm Bowel Dis, 14, 374–382.
Baumgart, D. C., & Sandborn, W. J. (2007). Inflammatory bowel disease: clinical
aspects and established and evolving therapies. Lancet, 369, 1641–1657.
Belluzi, A., Brignola, C., Campieri, M., Pera, A., Boschi, S., & Miglioli, M. (1996). Effect
of an enterical-coated fish-oil preparation on relapses in Crohn’s disease. N Engl J
Med, 334, 1557–1560.
Blumenthal M. editor. (2003). The ABC Clinical Guide to Herbs. 1st ed. Texas, American
Botanical Council.
Borreul, N., Carol, M., & Casellas, F. (2002). Increased mucosal turnout necrosis factor
alpha production in Crohn’s disease can be downregulated ex vivo by probiotic bacteria. Gut, 51, 659–64.
Braegger, C. R., Nicholls, S., & Murch, S. H. (1992). Tumour necrosis factor alpha in
stool as a marker of intestinal inflammation. Lancet, 339, 89–91.
Buddington, R. K., & Weiher, E. (1999). The application of ecological principles and
fermentable fibers to manage the gastrointestinal tract ecosystem. Journal of
Nutrition, 129, 1446S–1450S.
Buning, C., Geerdts, L., Fiedler, T., et al. (2006). DLG5 variants in inflammatory bowel
disease. Am J Gastroenterol, 101, 786–792.
Camacho-Barquero, L., Villegas, I., Sanchez-Calvo, J. M., et al. (2007). Curcumin, a
Curcuma longa constituent, acts on MAPK p38 pathway modulating COX-2
and iNOS expression in chronic experimental colitis. Int Immunopharmacol, 7(3),
333–342.
Chamaillard, M., Iacob, R., Desreumaux, P., & Colombel, J. (2006). Advances and perspectives in the genetics of inflammatory bowel diseases. Clin Gastroenterol Hepatol,
4, 143–51.
Cho, Judy. (2006). Genetic advances in inflammatory bowel disease. Curr Treat Options
Gastroenterol, 9, 191–200.
Cottone, M., Rosselli, M., Orlando, A. (1994). Smoking habits and recurrence in
Crohn’s disease. Gastroenterology, 106, 643–48.
Crohn’s and Colitis Foundation of America. (2007). What is Crohn’s Disease? Retrieved
November 8, 2007, from http://www.ccfa.org/info/about/crohns
Croucher, P. J., Mascheretti, S., & Hampe, J. (2003). Haplotype structure and association to Crohn’s disease of CARD15 mutations in two ethnically divergent populations. Eur J Hum Genet, 11, 6–16.
Ding, S., Minohara, Y., Fan, X. J., et al. (2007). Helicobacter pylori infection induces
oxidative stress and programmed cell death in human gastric epithelial cells. Infect
Immun, 75, 4030–4039.
Duggan, C., Ganno, J., & Walker, W. A. (2002) Protective nutrients and functional
foods for the gastrointestinal tract. Am J Clin Nutr, 75, 789–808.
Erdman, S., Fox, J. G., & Dangler, C. A. (2001). Typhiocolitis in NF-kappa B-deficient
mice. Journal of Immunology, 166, 1443–1447.
Faber, S. (2001). The treatment of abnormal gut flora improves symptoms in IBS
patients using IBS-QOL. American College of Gastroenterology 66th Annual
Scientific Meeting, May 28, 2001, Abstract 750369.
Ferguson, L., Shelling, A. N., Browning, B. L., Huebner, C., & Petermann, I. (2007)
Genes, diet and inflammatory bowel disease. Mutat Res, 622, 70–83.
Ferguson, L. R., Shelling, A. N., Lauren, D., et al. (2007). Nutrigenomics and gut health.
Mutat Res, 622, 1–6.
Fisher, S. A., Hampe, J., Onnie, C. M., et al. (2006). Direct or indirect association in a
complex disease: the role of SLC22A4 and SLC22A5 functional variants in Crohn
disease. Hum Mutat, 27, 778–785.
Fogg-Johnson, N., & Kaput, J. (2003) Nutrigenomics: an emerging scientific discipline.
Food Technol, 57, 60–67.
Galland, L. (2008) Gastroinstintal Dysregulation: Connections to Chronic Disease.
Gig Harbor, Institute for Functional Medicine.
Gasche, C., Scholmerich, J., & Brynskov, J. (2000). A simple classification of Crohn’s
disease: report of the Working Party for the World Congresses of Gastroenterology,
Vienna (1998). Inflamm Bowel Dis, 6, 8–15.
Gautam, S. C., Gao, X., & Dulchavsky, S. (2007). Immunomodulation by curcumin.
Adv Exp Med Biol, 595, 321–341.
Genova Diagnostics. (2007). Retrieved November 10, 2007 from http://www.gdx.net/
home/
Gerhardt, H., Seifert, F., Buvari, P., et al. (2001). Therapy of active Crohn disease with
Boswellia serrata extract H 15. Z Gastroenterol, 39(1), 11–17.
Gestel, G., Besancon, P., & Rouanet, J. M. (1994). Comparative evaluation of the effects
of two different forms of dietary fibre (rice bran vs. wheat bran) on rat colonic
mucosa and faecal microflora. Ann Nutr Metab, 38, 249–256.
Girardin, S. E., Boneca, I. G., & Viala, J. (2003). Nod2 is a general sensor of
peptidoglycan through muramyl depeptide (MDP) detection. J Biol Chem, 278,
8869–8872.
Griffin, S., Alderson, D., & Farndon, J. (1989). Acid resistant lipase replacement therapy
in chronic exocrine insufficiency: a study in dogs. Gut, 30, 1012–1015.
Go, V. L., Nguyen, C. T., Harris, D. M., & Lee, W. N. (2005). Nutrient-gene interaction:
metabolic genotype-phenotype relationship. J Nutr, 135, 3016S–3020S.
Gupta, I., Parihar, A., Malhotra, P., et al. (2001) Effects of gum resin of Boswellia serrata
in patients with chronic colitis. Planta Medica, 67(5), 391–395.
Gupta I, Parihar A, Malhotra P, et al. (1997) Effects of Boswellia serrata gum resin in
patients with ulcerative colitis. Eur J Med Res, 2(1), 37–43.
Halfvarson, J., Bresso, F., D’Amato, M., Jarnerot, G., Pettersson, S., & Tysk, C. (2005).
CARD15/NOD2 polymorphisms do not explain concordance of Crohn’s disease in
Swedish monozygotic twins. Dig Liver Dis, 37, 768–772.
Hampe, J., Cuthbert, A., Croucher, P. J., et al. (2001). Association between insertion
mutation in NOD2 gene and Crohn’s disease in German and British populations.
Lancet, 357, 1925–1928.
Han, P. D., Burke, A., Baldassano, R. N., Rombeau, J. L., & Lichtenstein, G. R. (1999).
Nutrition and inflammatory bowel disease. Gastroenterology Clinics of North
America, 28, 423–443.
Hanai, H., Iida, T., Takeuchi, K., et al. (2006). Curcumin maintenance therapy for
ulcerative colitis: randomized, multicenter, double-blind, placebo-controlled trial.
Clin Gastroenterol Hepatol, 4(12), 1502–1506.
Head, K. (2004). Inflammatory bowel disease part II: Crohn’s disease—pathophysiology
and conventional and alternative treatment options. Altern Med Rev, 9, 360–401.
Huemer, R editor. (1986) The Roots of Molecular Medicine: A Tribute To Linus Pauling.
New York, W. H. Freeman.
Hollander, D. (1988). Crohn’s disease: a permeability disorder of the tight-junction?
Gut, 29, 1621–1624.
Hollander, D. (1993). Permeability in Crohn’s disease: altered barrier functions in
healthy relatives? Gastoenterology, 104, 1848–1851.
Hollander, D. (1994). The importance of intestinal permeability in the pathogenesis of
Crohn’s disease. In Rachmilewitz, D. (Ed.), Inflammatory Bowel Diseases, Falk
Symposium 72. London: Kluwer Academic. (pp. 41–51).
Hollander, D. (1999). Intestinal permeability, leaky gut, and intestinal disorders. Curr
Gastroenterol Rep, 1, 410–416.
Hollander, D., Vadheim, C. M., Brettholz, E., et al. (1986). Increased intestinal permeability in Crohn’s patients and their relatives: an etiological factor. Ann Intern Med,
105, 883–885.
Hodges, L. S. (2005). Medical Nutrition Therapy for GI Disorders. In: Christie, C. (Ed.),
Manual of Medical Nutrition Therapy. Florida Dietetic Association, K2.1–K4.6.
Hoffbrand, A. V., Stewart, J. S., & Booth, C. C. (1968). Folate deficiency in Crohn’s disease: Incidence, pathogenesis, and treatment. Br Med J, 2, 71–75.
Holt, P. R., Katz, S., & Kirshoff, R. (2005). Curcumin therapy in inflammatory bowel
disease: a pilot study. Dig Dis Sci, 50(11), 2191–2193.
Human Genome Project Information. (2007). What is the Human Genome Project?
Retrieved November 18 , 2007 from http://www.ornl.gov/sci/techresources/
Human_Genome/home.shtml
Humbert, P., Russell, S., & Richardson, H. (2003). Dig, Scribble and Lgl in cell polarity,
cell proliferation and cancer. Bioessays, 25, 542–553.
Hugot, J. P., Chamaillard, M., Zouali, H., et al. (2001). Association of NOD2 leucinerich repeat variants with susceptibility to Crohn’s disease. Nature, 41, 599–603.
Inohara, N., Ogura, Y. & Fontalba, A. (2003). Host recognition of bacterial muramyl
dipeptide mediated through NOD2: implications for Crohn’s disease. J Biol Chem,
278, 5509–5512.
Inoue N., Tamura K., & Kinouchi Y. (2002). Lack of common NOD2 variants in
Japanese patients with Crohn’s disease. Gastroenterology, 123, 86–91.
Jess, T., Riis, L., Jespersgaard, C., et al. (2005). Disease concordance, zygosity, and
NOD2/CARD15 status: follow-up of a population-based cohort of Danish twins
with inflammatory bowel disease. Am J Gastroenterol, 100, 2486–2492.
Johnston, W. M. (2001). Probiotics Relieve IBS Symptoms Linked to Abnormal Gut
Flora. Gastroenterology and Endoscopy News, 38.
Jones, D. S. (Ed.). (2005). Textbook of Functional Medicine. Gig Harbor, WA: The
Institute for Functional Medicine.
Katz, K. D., Hollander, D., Vadheim, C. M. et al. (1989). Intestinal permeability
in patients with Crohn’s disease and their healthy relatives. Gastroenterology, 97,
927–931.
Kauwell, G. P. (2003). A genomic approach to dietetic practice. Are you ready? Top Clin
Nutr, 18, 81–91.
Kidd, P. (2003). Th1/Th2 Balance: the hypothesis, its limitations and implications for
health and disease. Altern Med Rev, 8, 223–246.
Kobayashi, K. S., Chamaillard, M., Ogura, Y., et al. (2005). Nod2-dependent regulation
of innate and adaptive immunity in the intestinal tract. Science, 307, 731–734.
Kozma, C. (2003). The interface between genomics and nutrition. Top Clin Nutr, 18,
73–80.
Kurup, V. P., Barrios, C. S., Raju, R., et al. (2007). Immune response modulation by
curcumin in a latex allergy model. Clin Mol Allergy, 5, 1.
Lashner, B. A., Shaheen, N. J., Hanauer, S. B., & Kirschner, B. S. (1993). Passive smoking
is associated with an increased risk of developing inflammatory bowel disease in
children. Am J Gastroenterol, 88, 356–359.
Lee, Y. H., Choi, S. J., Ji, J. D., Seo, H. S., & Song, G. G. (2000). Lipoprotein (a) and
lipids in relation to inflammation in rheumatoid arthritis. Clin Rheumatol, 19,
324–325.
Lerebours, E., Gower-Rousseau, C., Merle, V. et al. (2007). Stressful life events as a risk
factor for inflammatory bowel disease onset: A population-based case-control
study. Am J Gastroenterol, 102, 122–131.
Leong, R. W., Armuzzi, A., & Ahmad, T. (2003). NOD2/CARD15 gene polymorphisms
and Crohn’s disease in the Chinese population. Aliment Pharmacol Ther, 17,
1465–1470.
Lindberg, E., Jarnerot, G., & Huitfeldt, B. (1992). Smoking in Crohn’s disease: effect on
localisation and clinical course. Gut, 33, 779–782.
Liska, D. J., & Lukaczer, D. (2001). Gut dysfunction and chronic disease: the benefits of
applying the 4R GI restoration program. ANSR-Applied Nutrition Science Report,
Advanced Nutrition Publication, 1–8.
MacDonald, T. T. (2005). Immunity, inflammation, and allergy in the gut. Science, 307,
1920–25.
MacPherson, A., Khoo, U. Y., & Forgacs, I. (1996). Mucosal antibodies in inflammatory
bowel disease are directed against intestinal bacteria. Gut, 38, 365–375.
Mahmood, A., Fitzgerald, A. J., Marchbank T., et al. (2007). Zinc carnosine, a health
food supplement that stabilizes small bowel integrity and stimulates gut repair processes. Gut, 56, 168–175.
Malin, M., Suomalainen, H., Saxelin, M., & Isolauri, E. (1996). Promotion of IgA
immune response in patients with Crohn’s disease by oral bacteriotherapy with
Lactobacillus GG. Ann Nutr Metab, 40, 137–145.
Mathew, C. G., & Lewis, C. M. (2004). Genetics of inflammatory bowel disease: progress and prospects. Hum Mol Genet, 13, R161–168.
May, G. R., Sutherland, L. R., & Meddings, J. B. (1993). Is small intestinal permeability
really increased in relatives of patients with Crohn’s disease? Gastroenterology, 104,
1627–1623.
Mazmanian, S. K., Liu, C. H., Tzianabos, A. O., & Kasper, D. L. (2005). An immunomodulatory molecule of symbiotic bacteria directs maturation of the host immune
system. Cell, 122, 107–118.
Mitsushima, M., Sezaki, T., Akahane, R., et al. (2006). Protein kinase A-dependent
increase in WAVE2 expression induced by the focal adhesion protein vinexin. Genes
to Cells, 11, 281–92.
Mittermaier, C., Dejaco, C., Waldhoer, T., et al. (2004). Impact of depressive mood on
relapse inpatients with inflammatory bowel disease: a prospective 18-month followup study. Psychosom Med, 66, 79–84.
Motil, K. J., & Grand, R. J. (1985). Nutritional management of inflammatory bowel
disease. Pediatr Clin North Am, 32, 447–469.
Mullin, G. E., Maycon, Z. R., Sampat, A., et al. (1996). Intestinal mucosal lymphokine
production in Crohn’s disease has a Th1 profile. Inflamm Bowel Dis, 2, 16–26.
Muller, M., & Kersten, S. (2003). Nutrigenomics: goals and strategies. Nature Review/
Genetics, 4, 325–322.
Nakamura, H., Sudo, T., Tsuiki, H., et al. (1998). Identification of a novel human
homolog of the Drosophila dlg, P-dlg, specifically expressed in the gland tissues
and interacting with p55. FEBS Letters, 433, 63–67.
Neurath, M. F., Finotto, S., & Glimcher, L. H. (2002). The role of the Th1/Th2 polarization in mucosal immunity. Nat Med, 8, 567–573.
Ogura, Y., Bonen, D. K., Inohara, N., et al. (2001). A frameshift mutation in NOD2
associated with susceptibility to Crohn’s disease. Nature, 411, 603–606.
O’Hara, M. A., Kiefer, D., & Farrell, K. (1998). A review of 12 commonly used medicinal
herbs. Arch Fam Med, 7, 523–536.
OPASI: Office of Portfolio Analysis and Strategic Initiatives. NIH Roadmap for Medical
Research. Retrieved December 1, 2007 from http://nihroadmap.nih.gov/buildingblocks
Oriishi, T., Sata, M., Toyonaga, A., Sasaki, E., & Tanifawa, K. (1995). Evalution of intestinal permeability in patients with inflammatory bowel disease using lactulose and
measuring antibodies to lipid A. Gut, 36, 891–896.
O’Sullivan, M., & O’Morain, C. (2006). Nutrition in inflammatory bowel disease. Best
Pract Res Clin Gastroenterol, 20, 561–573.
Peltekova, V. D., Wintle, R. F., Rubin, L. A., et al. (2004). Functional variants of OCTN
cation transporter genes are associated with Crohn’s disease. Nat Genet, 2004, 36,
471–475.
Persson, P. G., Ahlbom, A., & Hellers, G. (1990). Inflammatory bowel disease and
tobacco smoke–a case-control study. Gut, 31, 1377–1381.
Plain, K., & Hotz, J. (1993). Therapeutic effects of Saccharomyces boulardii on mild
residual symptoms in a stable phase of Crohn’s disease with special respect to
chronic diarrhea–a pilot study. Gastroenterology, 31, 129–134.
Ramsay, R. R. (2000). The carnitine acyltransferases: modulators of acyl-CoAdependent reactions. Biochem Soc Trans, 28, 182–186.
Rath, H. C., Caesar, I., Roth, M., & Scholmerich, J. (1998). Nutritional deficiencies and
complications in chronic inflammatory bowel disease. Med Klin, 93, 6–10 (article in
German).
Rescigno, M., & Chieppa, M. (2005). Gut-level decisions in peace and war. Nat Med, 11,
254–255.
Riley, S. A., Mani, V., Goodman, M. J., et al. (1988). Comparison of delayed-release
5-ASA and sulfasalazine as maintenance treatment for patients with ulcerative colitis. Gastroenterology, 94, 1383–1389.
Roediger, W. E., & Nance, S. (1986). Metabolic induction of experimental ulcerative
colitis by inhibition of fatty acid oxidation. British Journal of Experimental,
Pathology, 67, 773–782.
Schreiber, S., Rosenstiel, P., Albrecht, M., Hampe, J., & Krawczak, M. (2005). Genetics
of Crohn’s disease, an archetypal inflammatory barrier disease. Nat Rev Genet, 6,
376–388.
Secondulfo, M. de Magistris, L., Fiandra, R., et al. (2001). Intestinal permeability in
Crohn’s disease patients and their first degree relatives. Dig Liver Dis, 33, 680–685.
Silverberg, M. S., Satsangi, J., & Ahmad, T. (2005). Toward an integrated clinical,
molecular and serological classification of inflammatory bowel disease: report of a
Working Party of the 2005 Montreal World Congress of Gastroenterology. Can J
Gastroenterol, 19 (supplement A), 5–36.
Shapiro, H., Singer, P., Halpern, Z., et al. (2007). Polyphenols in the treatment of
inflammatory bowel disease and acute pancreatitis. Gut, 56(3), 426–435.
Sharma, S., Chopra, K., Kulkarni, S. K., et al. (2007). Resveratrol and curcumin suppress immune response through CD28/CTLA-4 and CD80 co-stimulatory pathway. Clin Exp Immunol, 147(1), 155–163.
Singleton, J. W., Law, D. H., & Kelley, M. L. (1970). National Cooperative Crohn’s
Disease Study: Adverse reactions to drugs. Gastroenterology, 77, 870.
Somerville, K. W., Logan, R. F., Edmond, M., & Langman, M. J. (1984). Smoking and
Crohn’s disease. Br Med J (Clinical Research Edition), 289, 954–956.
Sonnenberg, A., McCarty, D.J., & Jacobsen, S. J. (1991). Geographic variation of inflammatory bowel disease within the United States. Gastroenterology, 100, 143–149.
Souba, W. W., Klimberg, V. S., & Plumley, D. (1990). The role of glutamine in maintaining a healthy gut and supporting the metabolic response to injury and infection.
J Surg Res, 48, 383–391.
Stoll, M., Corneliussen, B., Costello, C. M., et al. (2004). Genetic variation in DLG5 is
associated with inflammatory bowel disease. Nat Genet, 36, 476–480.
Sugimura, M., Kinouchi, Y., Takahashi, S., et al. (2003) CARD15/NOD2 mutational
analysis in Japanese patients with Crohn’s disease. Clin Genet, 63, 160–262.
Sutton, K. (2007). Considerations for the successful development and launch of personalized nutrigenomic foods. Mutat Res, 622, 117–221.
Teahon, K., Roseth, A., Foster, R., & Bjarnason, I. (1997). Faecal calprotectin: a simple
sensitive quantitative measure of intestinal inflammation in man [abstract]
Gastroenterology, 112(supplement), A1103.
Tibble, J. A., Sigthorsson, G., & Bjarnason, I. (1999). High prevalence of NSAID
enteropathy as shown by a simple faecal test. Gut, 45, 362–366.
Tokuhiro, S. (2003). An intronic SNP in a RUNX1 binding site of SLC22A4, encoding
an organic cation transporter, is associated with rheumatoid arthritis. Nat Genet, 35,
341–348.
Vermeire, S., & Rutgeerts, P. (2004). Antibody responses in Crohn’s disease.
Gastroenterology, 126, 601–604.
Wakabayashi, M. (2003). Interaction of Ip-dlg/KIAA0583, a membrane-associated
guanylate kinase family protein, with vinexin and beta-catenin at sites of cell-cell
contact. J Bio Chem, 278, 21709–21714.
Whitney, E. N., Cataldo, C. B., & Rolfes, S. R. (1998). Understanding Normal and
Clinical Nutrition. 5th ed. Belmont, CA: West/Wadsworth.
Wikipedia. Retrieved November 8, 2007 from http://en.wikipedia.org/wiki/Scaffold_
protein